Diuretic efficiency of a single dose of subcutaneous versus oral furosemide after heart failure hospitalization across diuretic resistance strata: A pilot randomized controlled trial

Aims: Diuretic resistance (DR) in heart failure (HF) is associated with worse outcomes. Furoscix®, a self-administered subcutaneous (sc) furosemide injection administered via on-body infusor, is approved for HF congestion relief. However, its efficacy in patients with DR post-HF hospitalization remains unknown. Methods and results: In this open-label pilot randomized controlled trial, 70 participants were randomized within 14 days post-HF hospitalization to receive a single dose of 80 mg sc furosemide or home oral dose furosemide. Enrolment was stratified by presence of DR (admission BAN-ADHF score ≥12) with a 2:1 enrolment of those with versus without DR. Key outcomes included diuretic efficiency, the total urine output per mg of diuretic administered, and peak urine sodium within 8 h of dose administration. Treatment effects were calculated as the difference in estimated marginal means across study groups and DR strata using linear mixed-effect models. Overall, 70 participants were enrolled (57 years, 27% female, 70% Black, 79% with HF with reduced ejection fraction). Participants with DR (n = 46) had worse kidney function, higher N-terminal pro-B-type natriuretic peptide, and higher home diuretic dose. Among participants with DR, sc furosemide versus oral furosemide led to significantly greater diuretic efficiency (34.0 vs. 22.6 ml/mg, p = 0.002) and peak urine sodium (100 vs. 83 mmol/L, p = 0.029), while participants without DR had similar diuretic efficiency (29.8 vs. 30.1 ml/mg, p = 0.94) and peak urine sodium (96 vs. 95 mmol/L, p = 0.93) across both treatments. DR significantly modified the effect of sc versus oral furosemide on diuretic efficiency (p_interaction: treatment × diuretic resistance = 0.022). Conclusion: Single-dose sc furosemide was associated with greater diuretic efficiency and peak urine sodium than oral furosemide in participants with DR discharged following recent HF hospitalization.